Azithromycin is a macrolide antibiotic which has the formula:

Azithromycin is chemically described as (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-O-methyl-α-L-ribo-hexo-pyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin has the molecular formula C38H72N2O12, and has a molecular weight of 749.00.
Azithromycin is approved in the United States for the treatment of community-acquired pneumonia and pelvic inflammatory disease when caused by susceptible organisms, such as Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes, Haemophilus ducreyi, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Chlamydia pneumoniae, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma hominis, and Mycoplasma pneumoniae. 
Azithromycin is supplied in lyophilized form under vacuum in a 10-mL vial equivalent to 500 mg of azithromycin for intravenous administration (e.g., marketed by Pfizer under the trade name Zithromax®). Each vial also contains sodium hydroxide and citric acid. For therapeutic applications, the lyophilized azithromycin is reconstituted with a sterile aqueous vehicle such as Sterile Water for Injection, USP, and is administered by injection. Typically, the 500 mg dosage form is reconstituted with 4.8 mL of the aqueous vehicle to achieve a concentration of about 100 mg/nL. Solutions of azithromycin may be diluted further in injectable fluids such as Normal Saline (0.9% sodium chloride), ½ Normal Saline (0.45% sodium chloride), 5% Dextrose in Water, Lactated Ringer's Solution, 5% Dextrose in ½ Normal Saline with 20 mEq KCl, 5% Dextrose in Lactated Ringer's Solution, 5% Dextrose in ⅓ Normal Saline, 5% dextrose in ½ Normal Saline, Normosol®-M in 5% Dextrose, and Normosol®-R in 5% Dextrose.
Azithromycin is normally administered via intravenous (i.v.) injection at a dosage of 500 mg per day for one to two days. Intravenous therapy typically is followed by oral administration of azithromycin at a single daily dose of 500 mg or 250 mg, to complete a 7-10 day course of therapy. Reconstituted azithromycin solution is stable for 24 hours when stored below 30° C. or 86° F. When diluted to 1.0-2.0 mg/mL, azithromycin for injection is stable for 24 hours at or below room temperature (30° C. or 86° F.), or for 7 days if stored under refrigeration (5° C. or 41° F.).
Current approaches for manufacturing lyophilized forms of azithromycin utilize the dihydrate form of azithromycin (see, e.g., U.S. Pat. No. 6,268,489). There remains a need for a stable, sterile form of lyophilized azithromycin and for efficient methods of producing such a formulation. The invention provides such a formulation and methods. These and other advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.